Polychlorinated biphenyls (PCBs) are widespread contaminants that have been demonstrated to have neurotoxic properties. We have recently shown that, following exposure to complex mixtures of PCBs, brain biogenic amines, an important class of neurotransmitters, involved in the control of learning, motor and emotional behaviors are significantly altered. Furthermore only a small number of congeners accumulate in rat brain, suggesting that the observed PCB neurotoxicity may be due to a small fraction of the congeners that exist in the environment. We now propose to determine neurochemical alterations of central nervous system function in non-human primates following exposure to: (1) lightly and heavily chlorinated PCB mixtures (Aroclor 1016 and Aroclor 1260); and (2) individual congeners that will be shown by chemical analysis to accumulate in non-human primate brain. Measures will include alterations in concentrations of the biogenic amines and their major metabolites in urine, plasma, cerebrospinal fluid and post-mortem brain, determined by high-performance liquid chromatography. Serum, fat-biopsy and post-mortem brain PCB concentrations, as determined by congener-specific glass capillary gas chromatographic techniques, will also be measured during and following exposure to the PCBs. These measures will determine, in a species more neurologically and toxicologically similar to man than the rat: (a) the neurotoxicity of lightly versus heavily chlorinated PCB mixtures; (b) the neurotoxicity of PCB congeners which will be found to accumulate in non-human primate brain; (c) the persistence of neurochemical change following cessation of PCB exposure, and (d) the ability to predict neurochemical change based on previously established PCB structure-activity functions. Information gathered from these experiments will substantially increase the ability to predict the risk of environmental or occupational exposure of humans to complex PCB mixtures, determine the neurotoxicity of PCB congeners that accumulate in human biological systems and determine if previously developed structure-activity relationships of PCB congeners are of value in predicting neurochemical change.